Hypophosphatemic rickets (previously called vitamin D-resistant rickets) is a disorder in which the bones become painfully soft and bend easily because the blood contains low levels of phosphate and has inadequate amounts of the active form of vitamin D.[1] The condition can be caused by mutations in the phosphate-regulating endopeptidase gene, also known as the PHEX gene and is nearly always inherited.[2] The aim of treatment is to raise phosphate levels in the blood, which will promote normal bone formation. Phosphate can be taken by mouth and should be combined with calcitriol, the activated form of vitamin D.[1]

Last updated: 9/17/2009

What causes hypophosphatemic rickets?

Hypophosphatemic rickets is nearly always hereditary.[1] The specific gene involved determines the way it is inherited. X-linked hypophosphatemic (XLH) rickets is caused by mutations in the phosphate-regulating endopeptidase gene (PHEX) located on chromosome Xp22.2-p22.1.[2] Autosomal dominant hypophosphatemic rickets (ADHR) is caused by mutations in a gene encoding a member of the fibroblast growth factor family, FGF23, on chromosome 12p13.[3] Autosomal recessive hypophosphatemic rickets (ARHR) is caused by mutations in the DMP1 gene on chromosome 4q21.[4] An X-linked recessive form is caused by mutations in the CLCN5 gene at Xp11.22.[5]

The genetic defect causes a kidney abnormality that allows an inappropriately high amount of phosphate to be excreted into the urine, resulting in low levels of phosphate in the blood. Because bones need phosphate for growth and strength, this deficiency causes defective bones. In rare cases, the disorder develops as a result of certain cancers, such as giant cell tumors of bone, sarcomas, prostate cancer, and breast cancer.[1]

Because I have hypophosphatemic rickets, are my children at risk to suffer the same disorder?

Hypophosphatemic rickets is a genetic condition. This puts your offspring at risk to inherit the mutation which causes the disease. To learn more about the specific risks to your future children, we recommend that you consult with a genetics professional.

Last updated: 9/17/2009

How can I find a genetics professional in my area?

Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about genetic consultations is available from Genetics Home Reference. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:

The American Society of Human Genetics maintains a database of its members, which includes individuals who live outside of the United States. Visit the link to obtain a list of the geneticists in your country, some of whom may be researchers that do not provide medical care.